Small molecule tyrosine kinase inhibitors and monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) are widely used for a variety of solid tumors. Even though these treatments are tolerated well, dermatological toxicities pose major problems: An acneiform rash affects 70 to 90 percent of patients; dry skin, up to 100%; pruritus, 33%; paronychia, 56%; hair loss, 50%; and hair growth changes, 88%.
Skin being the largest organ in the body, these side effects can affect quality of life significantly. It is important that we learn how to manage these problems well. I will describe here my own approach.
The papulopustular rash occurs within the first eight weeks in the majority of patients. Based on the results from randomized studies, I use prophylactic minocycline 100 mg once daily or a combined regimen of doxycycline 100 mg bid, hydrocortisone 1% cream to the face and chest, sunscreen, and a moisturizer daily starting from day 1 of therapy, even before rash appears.
I find them to be quite effective in reducing the severity and frequency of Grade $2 skin toxicities by more than 50%.
I continue this regimen daily from day 1 of starting EGFR- directed therapy until the sixth week of therapy. If the rash persists, I will continue for an additional four weeks and then re-evaluate our patients.
I have a low threshold for performing bacterial cultures in areas of rash. I want to point out that in a study of 228 patients treated with EGFR inhibitors, up to 38% of these patients developed infections at sites of skin toxicities. Bacterial infections were the most common, followed by viral and fungal infections. I tend to tailor my antibiotics based on the culture results from these swabs.
It has been my experience that nearly everyone will develop dry skin after several months of EGFR- inhibitor therapy. For the face, I use a gentle moisturizer, such as Eucerin cream. For the body, I recommend Aveeno, Cetaphil, or CeraVe creams to be applied within 15 minutes of showering. I advise my patients that skin should be patted dry with a towel before.
For dry skin in the fingertips or heels with thickening and scaling, Ii would recommend an exfoliant such as Lac-Hydrin or Salex cream to the palms and soles.
For fissures in the fingertips, I use Desitin Maximum Strength three times a day. I would also ask my patients to wear cotton socks and gloves at bedtime over the cream.
Since dryness inside the nose usually represents Staphylococcus aureus colonization, I use mupirocin 2% ointment twice daily for two weeks.
As for xerotic dermatitis, (dry skin becoming painful and red) I recommend a topical steroid such as triamcinolone 0.1% cream twice daily. As always in these patients, I would suspect secondary infections in painful areas, especially if there is any yellow crusting or discharge. A bacterial swab culture is recommended to determine culprit and sensitivities.
Painful paronychia in the fingers or toes occurs in 56% of people treated with EGFR inhibitors. When mild to moderate paronychia develops, I use topical mupirocin 2% ointment and fluocinonide 0.05% bid.
For severe or discharging paronychia with pain, I also recommend soaking fingers or toes in a solution of white vinegar in tap water for 15 minutes every night. Silver nitrate chemical cauterization done weekly is helpful when pain is present.
I usually do it the first time so the patient can see how it is done, and give a prescription so that they can do it at home. For demonstration on how to do this, see this video: http://bit.ly/jG7PWq.
Cultures should be obtained of draining areas for possible secondary infections. Also I recommend soft cotton gloves when performing activities and wearing soft padded shoes and slippers (Tempurpedic slippers, Crocs).
Itching is very common, and can occur either on intact skin, or in skin affected by rash or dryness. If the characteristic rash underlies itching, I recommend treating the rash with an oral antibiotic (doxycycline or minocycline 100 mg bid for 4-6 weeks), along with a topical steroid such as triamcinolone 0.1% (Kenalog, Aristocort) or mometasone 0.1% (Elocon) creams twice daily.
Over-the-counter anti-itch creams such as Aveeno Anti-Itch cream or Sarna Ultra Cream are good for the body. For generalized itching that affects quality of life or sleep, systemic antihistamines are useful—I would try a non-sedating antihistamine during the day (Zyrtec, Allegra) and Benadryl or Atarax in the evening (this could also help with sleep).
For topic steroids for the face, I recommend hydrocortisone 2.5% (Hytone) or alclometasone 0.5% (Aclovate) cream twice daily for up to eight weeks. After that, a reevaluation of the severity of rash is recommended to determine continued therapy.
For the body, triamcinolone 0.1% (Kenalog, Aristocort) or mometasone 0.1% (Elocon) creams twice daily, also for up to eight weeks.
And for the scalp, use Clobex solution or shampoo since hair-bearing areas are not amenable to treatment with creams or ointments.
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